We will utilize two carcinogens of different chemical classes: 1) diethylnitrosamine, an alkylating agent; 2) N-2-fluorenylacetamide, an aromatic amide. We will attempt to correlate alterations in three modalities with the crucial sequences in malignant evolution; a) morphology - light and electron microscopy, histochemistry; b) chromosomal composition; c) alpha fetoprotein production. In addition, we will continue to examine and expand our investigation of the capacity of carcinogen-exposed tissues to "activate" carcinogens as evidenced by mutagenic capacity. Further studies of the alternation of DNA by base-analysis will be pursued using HPLC technology. Each of these modalities may give information concerning alteration of DNA as related to the "phases" described by biologic means. BIBLIOGRAPHIC REFERENCES: Becker, F.F.: Sequential phenotypic and biochemical alterations during chemical hepatocarcinogenesis. Cancer Research, 36:2563-2566, 1976. Becker, F.F., D. Stillman, and S. Sell: Serum alpha-fetoprotein in a mouse strain (C3H-Avyfb) with spontaneous hepatocellular carcinomas. Cancer Research, 37:870-872, 1977.